Colorectal cancer continues as the third leading cause of cancer death in both males and females in the United States. Data from the National Poly Study show that repeated colonoscopic surveillance with United States. Data from the National Poly Study show that repeated colonoscopic surveillance with removal of any discovered adenomas reduces colonic cancer occurrence; however, the results also show that adenoma recurrence is common (>40% at 3 years), that compliance with scheduled follow-up colonoscopic examinations is problematic and that the cost is significant for the cancer prevention achieved. Clearly, there is a need to develop dietary and chemopreventive intervention strategies that can be applied to large populations to reduce both adenoma recurrence and colorectal cancer risk. In Project 1a, we focus on reducing the risk of adenoma recurrence by lowing the relative concentration of deoxycholic acid, a putative tumor promoting secondary bile acid in fecal contents, through the use of ursodeoxycholic acid and in Project 1b, by changing intrinsic colon mucosal cell metabolic pathways with a drug, celecoxib )A COX-2 inhibitor), and a nutritional supplement, selenium (formulated in baker's yeast), that can modify elements of signal transduction pathways that are thought to affect neoplastic progression. The use of all three of these exciting chemopreventive agents are supported by strong epidemiologic, preclinical and preliminary clinical data and all appear to have excellent safety profiles. Project 1a completes an ongoing, placebo- controlled, double-blind, cancer control, phase III study of ursodeoxycholic acid in participants with a recent history of resected colorectal adenomas. Enrollment of the required 1200 participants was achieved in the late fall 1999. The rates of participants going off drug treatment and the occurrence of significant adverse events are exceptionally low. All participants and data processing aspects of the study will be completed within the next four years. Project 1b is a new placebo-controlled, double-blind, phase II trial of factorial design, evaluating prevention of recurrent colon adenomas by treatment with the COX-2 inhibitor, celecoxib, or selenium in the form of baker's yeast, or a combination of the two agents versus placebo The study will be conducted in 1,600 evaluable participants with a history of resected adenomas chosen to be similar to those evaluated in the Project 1a ursodeoxycholic acid study. A major strength obtained by using a comparable study design and participants (n=2,800) will be the opportunity to evaluate several risk factors that may affect polyp recurrence, progression and response to intervention, in this large study population.